Extracellular vesicles from adipose-derived mesenchymal stem cells down-regulate senescence features in osteoarthritic osteoblasts

Tofiño-Vian, Miguel, Maria Isabel Guillén, María Dolores Pérez del Caz, and Miguel Angel.

Abstract Osteoarthritis (OA) affects all articular tissues leading to pain and disability. The dysregulation of bone metabolism may contribute to the progression of this condition. Adipose-derived mesenchymal stem cells (ASC) are attractive candidates in the search of novel strategies for OA treatment and exert anti-inflammatory and cytoprotective effects on cartilage. Chronic inflammation in OA is a relevant factor in the development of cellular senescence and joint degradation. In this study, we extend our previous observations of ASC paracrine effects to study the influence of conditioned medium and extracellular vesicles from ASC on senescence induced by inflammatory stress in OA osteoblasts. Our results in cells stimulated with interleukin(IL)-1β indicate that conditioned medium, microvesicles and exosomes from ASC down-regulate senescence-associated β-galactosidase activity and the accumulation of γH2AX foci. In addition, they reduced the production of inflammatory mediators, with the highest effect on IL-6 and prostaglandin E2. The control of mitochondrial membrane alterations and oxidative stress may provide a mechanism for the protective effects of ASC in OA osteoblasts. We have also shown that microvesicles and exosomes mediate the paracrine effects of ASC in these cells. Our study suggests that correction of abnormal osteoblast metabolism by ASC products may contribute to their protective effects in joint degradation.


 Keywords: adipose-derived mesenchymal stem cells, osteoblast, senescence, inflammation, oxidative stress, osteoarthritis

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